Adagrasib (MRTX849)

Catalog No.S8884 Batch:S888405

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Technical Data

Formula

C32H35ClFN7O2
Molecular Weight 604.12 CAS No. 2326521-71-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (165.53 mM)
Ethanol 100 mg/mL (165.53 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Adagrasib (MRTX849) is a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C and inhibits KRAS-dependent signaling.
Targets
K-Ras(G12C) [1]
In vitro

To evaluate the breadth of MRTX849 activity, its effect on cell viability is determined across a panel of 17 KRASG12C-mutant and three non-KRASG12C-mutant cancer cell lines using 2D (3-day, adherent cells) and 3D (12-day, spheroids) cell growth conditions. MRTX849 potently inhibits cell growth in the vast majority of KRASG12C-mutant cell lines with IC50 values ranging between 10 nM and 973 nM in the 2D format and between 0.2 nM and 1042 nM in the 3D format.[1].
In vivo

Rapid tumor regression is observed at the earliest posttreatment tumor measurement and animals in the 30 mg/kg and 100 mg/kg cohorts exhibits evidence of a complete response at study Day 15. Dosing is stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remains tumor-free through study Day 70.[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    MIA PaCa-2, H1373, H358, H2122, SW1573, H2030, KYSE-410 cells (G12C); H1299 (WT); A549 (G12S), HCT116 (G13D) cells

  • Concentrations

    --

  • Incubation Time

    24 h

  • Method

    All cell lines were maintained at 37 ℃ in a humidified incubator at 5% CO2 and were periodically checked for mycoplasma. CellTiter-Glo assay to evaluate cell viability performed on seven KRAS G12C-mutant cell lines and three non-KRAS G12C-mutant cell lines cells grown in 2D tissue culture conditions in a 3-day assay or 3D conditions using 96-well, ULA plates in a 12-day assay.
Animal Study:

[1]
  • Animal Models

    MIA PaCa-2 model

  • Dosages

    3 mg/kg, 10 mg/kg, 30 mg/kg and 100 mg/kg

  • Administration

    Oral gavage

Selleck's Adagrasib (MRTX849) has been cited by 14 publications

Base editing screens define the genetic landscape of cancer drug resistance mechanisms [ Nat Genet, 2024, 10.1038/s41588-024-01948-8] PubMed: 39424923
Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer [ Nat Commun, 2024, 15(1):6076] PubMed: 39025835
AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692] PubMed: 38342232
ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma [ bioRxiv, 2024, 2024.10.04.616725] PubMed: 39416034
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma [ Cancer Discov, 2023, 13(4):880-909] PubMed: 36700848
Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers [ Mol Cancer Ther, 2023, 22(12):1422-1433] PubMed: 37703579
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction [ bioRxiv, 2023, 2023.03.03.531059] PubMed: 36945559
Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy [ Cancer Discov, 2022, CD-22-1074] PubMed: 36250888
Integrated analysis of the tumor microenvironment using a reconfigurable microfluidic cell culture platform [ FASEB J, 2022, 36(10):e22540] PubMed: 36083096
Development of a biotin-streptavidin-enhanced enzyme-linked immunosorbent assay (BA-ELISA) for high-throughput screening of KRASG12C inhibitors [ SLAS Discov, 2022, 27(2):107-113] PubMed: 35058184

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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